RESUMEN
BACKGROUND: This study aimed to perform a comprehensive pooled analysis of all published series involving pediatric patients with large vessel occlusion (LVO) undergoing endovascular treatment (EVT) to study the disease landscape including presentation, management, and outcomes. METHODS: The data used in this study were pooled from published literature on EVT for pediatric stroke spanning from 1980 to 2023. The relevant articles were carefully reviewed, and only those reporting at least one case of pediatric LVO undergoing EVT were included. Furthermore, pediatric patients with LVO who received EVT from the Chinese Pediatric Ischemic Stroke Registry database were also included. The primary outcome for this study was the unfavorable outcome after stroke. The risk factors influencing the outcomes of patients with pediatric stroke treated with EVT were analyzed using Cox proportional hazards models. RESULTS: A total of 221 pediatric patients who underwent EVT were included. During an average follow-up period of 6 months, 20.8% of patients had an unfavorable outcome. Multivariate Cox regression showed that patients with a higher Pediatric National Institutes of Health Stroke Scale (pedNIHSS) score (aHR=7.54, 95% CI 2.38 to 23.58) and unsuccessful reperfusion (aHR=5.84, 95% CI 2.86 to 11.93) were associated with an increased risk of unfavorable outcomes, while older age (aHR=0.27, 95% CI 0.09 to 0.82) was associated with a lower risk of unfavorable outcomes. CONCLUSION: Following EVT treatment, a significant proportion of pediatric patients with LVO achieved favorable outcomes. However, factors such as the severity of the pedNIHSS score and unsuccessful reperfusion were found to be associated with a poorer prognosis.
RESUMEN
An intramolecular organocatalytic cascade dearomatizing spirocycloaddition reaction of indole-ynone compounds containing O-silyl-naphthol substituents has been developed with the use of a chiral bifunctional thiourea. This process was able to provide various structurally diverse polycyclic spiroindolines in high yields (up to 98%) with excellent stereoselectivities (>20:1 dr, up to 98% ee) involving the formation of carbonylvinylidene ortho-quinone methide intermediates.
RESUMEN
Fluorene derivatives have been widely developed in OLEDs because of its efficient fluorescence quantum efficiency, but for which unique rigid biphenyl planar structure and large conjugated system, we hypothesize that they have a great potential for room temperature phosphorescence (RTP) applications, and confirmed this conjecture by subjecting polyvinyl alcohol (PVA) and phosphors to thermal annealing. The cross-linked structure formed during thermal annealing judiciously modulates the phosphorescence emission characteristics of the fluorenol with the synergistic interaction between PVA and fluorenol. Specifically, the lifetime exhibited a substantial increase from 1352.2â ms to 2874.1â ms, accompanied by a quantum yield augmentation from 4.8 % to 11.3 %, which substantiate that cross-linked induced by thermal annealing effectively amplifies the phosphorescent intensity and stability of the phosphors, facilitating ultralong phosphorescent emission at ambient conditions. Furthermore, an effective probe based on this film is developed for its highly sensitive, quantitative and immediate detection of volatile organic compounds. This investigation not only proffers a novel paradigm for the development of advanced RTP materials but also imparts insightful considerations for optimizing the performance of polymers in conjunction with functional materials, encompassing bioimaging, sensing, and optoelectronic devices.
RESUMEN
Endoplasmic reticulum stress (ERS) and oxidative stress (OS) are adaptive responses of the body to stressor stimulation. Although it has been verified that Trichinella spiralis (T. spiralis) can induce ERS and OS in the host, their association is still unclear. Therefore, this study explored whether T. spiralis-secreted serpin-type serine protease inhibitor (TsAdSPI) is involved in regulating the relationship between ERS and OS in the host intestine. In this study, mice jejunum and porcine small intestinal epithelial cells (IECs) were detected using qPCR, western blotting, immunohistochemistry (IHC), immunofluorescence (IF), and detection kits. The results showed that ERS- and OS-related indexes changed significantly after TsAdSPI stimulation, and Bip was located in IECs, indicating that TsAdSPI could induce ERS and OS in IECs. After the use of an ERS inhibitor, OS-related indexes were inhibited, suggesting that TsAdSPI-induced OS depends on ERS. When the three ERS signalling pathways, ATF6, IRE1, and PERK, were sequentially suppressed, OS was only regulated by the PERK pathway, and the PERK-eif2α-CHOP-ERO1α axis played a key role. Similarly, the expression of ERS-related indexes and the level of intracellular Ca2+ were inhibited after adding the OS inhibitor, and the expression of ERS-related indexes decreased significantly after inhibiting calcium transfer. This finding indicated that TsAdSPI-induced OS could affect ERS by promoting Ca2+ efflux from the endoplasmic reticulum. The detection of the ERS and OS sequences revealed that OS occurred before ERS. Finally, changes in apoptosis-related indexes were detected, and the results indicated that TsAdSPI-induced ERS and OS could regulate IEC apoptosis. In conclusion, TsAdSPI induced OS after entering IECs, OS promoted ERS by enhancing Ca2+ efflux, and ERS subsequently strengthened OS by activating the PERK-eif2α-CHOP-ERO1α axis. ERS and OS induced by TsAdSPI synergistically promoted IEC apoptosis. This study provides a foundation for exploring the invasion mechanism of T. spiralis and the pathogenesis of host intestinal dysfunction after invasion.
Asunto(s)
Estrés del Retículo Endoplásmico , Células Epiteliales , Estrés Oxidativo , Serpinas , Trichinella spiralis , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Trichinella spiralis/fisiología , Ratones , Estrés Oxidativo/efectos de los fármacos , Porcinos , Serpinas/metabolismo , Serpinas/genética , Inhibidores de Serina Proteinasa/farmacología , Proteínas del Helminto/metabolismo , Proteínas del Helminto/genética , Yeyuno/efectos de los fármacosRESUMEN
Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.
Asunto(s)
Diabetes Mellitus Experimental , Vesículas Extracelulares , Fibroblastos , Queratinocitos , ARN Circular , Cicatrización de Heridas , Animales , Humanos , Masculino , Ratones , Ratas , Movimiento Celular , Proliferación Celular , Modelos Animales de Enfermedad , Vesículas Extracelulares/química , Fibroblastos/efectos de los fármacos , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genética , Queratinocitos/efectos de los fármacos , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , ARN Circular/farmacología , ARN Circular/uso terapéutico , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND: Current studies on the impact of sex in the prognosis of childhood arterial ischemic stroke (AIS) are limited. We aimed to explore the sex differences in outcomes in patients with childhood AIS. METHODS: A retrospective analysis was conducted using the prospective data from the Chinese Pediatric Ischemic Stroke Registry. Baseline characteristics between sexes were compared in the total population cohort, propensity score (PS)-matched cohort, and inverse probability of treatment weighting cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was applied to further analyze the improvement in pediatric modified Rankin Scale (mRS) scores between sexes from 90 days to one year. Survival analysis was used to estimate the recurrence rates during the follow-up period. RESULTS: A total of 468 patients were finally included. Multivariate logistic regression showed that there were no significant differences between females and males in achieving favorable outcome (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.63 to 1.72), functional independence (OR 0.98, 95% CI 0.59 to 1.63), or shift to worse pediatric mRS scores (OR 0.83, 95% CI 0.59 to 1.17) at 90-day. Mixed-effects regression and survival analysis indicated that females and males exhibited comparable functional recovery from 90 days to one year and had similar recurrent risk during the follow-up period. CONCLUSIONS: This nationally-representative observational study indicated that both male and female pediatric patients with AIS exhibited comparable similar clinical outcomes at 90 days, as well as similar improvements and risks of recurrence during the follow-up period.
Asunto(s)
Accidente Cerebrovascular Isquémico , Sistema de Registros , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , China/epidemiología , Pueblos del Este de Asia , Accidente Cerebrovascular Isquémico/epidemiología , Pronóstico , Estudios Retrospectivos , Factores SexualesRESUMEN
1,2-Bis(diphenylphosphino)ethanes (DPPEs) are versatile and immensely important ligands in transition metal catalysts. Here we report the dithiophosphinylation of readily available allenyl acetates to give DPPEs in high yields and regioselectivity. This protocol features a broad substrate scope and mild conditions, avoiding the use of transition metals and air-sensitive sources of phosphorus. Mechanism studies indicate that the reaction was accomplished via an SN2'-type addition-elimination followed by a 1,4-addition step.
RESUMEN
Sex pheromone analogs have high structural similarity to sex pheromone components. They also play a role in studying many agricultural pests. In our study, (Z, Z, Z)-3,6,9-nonadecadiene (Z3Z6Z9-19:Hy) was successfully synthesized, which is an analogue to 1 of 2 sex pheromone components of Ectropis grisescens Warren (Z, Z, Z)-3,6,9-octadecatriene (Z3Z6Z9-18:Hy), and it showed potential inhibition in experiments. In the electroantennogram test, Z3Z6Z9-19:Hy showed a dose-dependent response, and only measured half the response of Z3Z9-6,7-epo-18:Hy. However, the compound significantly reduced positive response of E. grisescens males by up to 70% in the Y-tube olfactometer. Furthermore, in the wind tunnel, it significantly inhibited all types of behavioral responses. The percentage of moths contacting the pheromone odor source was reduced even at the lowest dose tested. In silico study afterward, molecular docking results showed affinity between Z3Z6Z9-19:Hy and sensory neuron membrane protein 1. Our study revealed the potential of Z3Z6Z9-19:Hy as a sex pheromone inhibitor, which would provide new tools for monitoring and mating disruption of E. grisescens.
Asunto(s)
Antenas de Artrópodos , Mariposas Nocturnas , Atractivos Sexuales , Animales , Atractivos Sexuales/farmacología , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/fisiología , Masculino , Antenas de Artrópodos/fisiología , Antenas de Artrópodos/efectos de los fármacos , Femenino , Alcadienos , Simulación del Acoplamiento Molecular , Simulación por ComputadorRESUMEN
The spontaneous centrosymmetry-breaking and robust room-temperature ferroelectricity in niobium oxide dihalides spurs a flurry of explorations into its promising second-order nonlinear optical properties, and promises potential applications in nonvolatile electro-optical and optoelectronic devices. However, the ambient stability of the niobium oxide dihalides remains questionable, which overshadows their future development. In this work, the chemical degradation of NbOI2 is comprehensively investigated using combined chemical and optical microscopies in conjunction with spectroscopies. We unveil the highly anisotropic degradation kinetics of NbOI2 driven by the hydrolysis process of the unstable dangling iodine bonds dominantly on the (010) facet and progressing along the c axis. Knowing its degradation mechanism, the NbOI2 flake can then be stabilized by the hexagonal boron nitride encapsulation, which isolates the air moisture. These findings provide direct insights into the ambient instability of NbOI2, and they deliver possible solutions to circumvent this issue, which are essential for its practical integration in photonic and electronic devices.
RESUMEN
Cellular senescence is closely associated with the pathogenesis of sepsis. However, the diagnostic and prognostic value of senescence-related genes remain unclear. In this study, 866 senescence-related genes were collected from CellAge. The training cohort, GSE65682, which included 42 control and 760 sepsis samples, was obtained from the Gene Expression Omnibus (GEO). Feature selection was performed using gene expression difference detection, LASSO analysis, random forest, and Cox regression. TGFBI and MAD1L1 were ultimately selected for inclusion in the multivariate Cox regression model. Clustering based on the expressions of TGFBI and MAD1L1 was significantly associated with sepsis characteristics and prognoses (all P < 0.05). The risk signature served as a reliable prognostic predictor across the GSE65682, GSE95233, and GSE4607 cohorts (pooled hazard ratio = 4.27; 95% confidence interval [CI] = 1.63-11.17). Furthermore, it also served as a robust classifier to distinguish sepsis samples from control cases across 14 cohorts (pooled odds ratio = 5.88; 95% CI = 3.54-9.77). Single-cell RNA sequencing analyses from five healthy controls and four sepsis subjects indicated that the risk signature could reflect the senescence statuses of monocytes and B cells; this finding was then experimentally validated in THP-1 and IM-9 cells in vitro (both P < 0.05). In all, a senescence-related gene signature was developed as a prognostic and diagnostic biomarker for sepsis, providing cut-in points to uncover underlying mechanisms and a promising clinical tool to support precision medicine.
Asunto(s)
Sepsis , Humanos , Pronóstico , Sepsis/diagnóstico , Sepsis/genética , Análisis de la Célula Individual , Análisis de Secuencia de ARN , BiomarcadoresRESUMEN
Long-persistent luminescent (LPL) materials have attracted considerable research interest due to their extensive applications and outstanding afterglow performance. However, the performance of red LPL materials lags behind that of green and blue materials. Therefore, it is crucial to explore novel red LPL materials. This study introduces a straightforward and viable strategy for organic-inorganic hybrids, wherein the organic ligand 1,3,6,8-Tetrakis(4-carboxyphenyl)pyrene (TCPP) is coordinated to the surface of a red persistent phosphor Sr0.75 Ca0.25 S:Eu2+ (R) through a one-step method. TCPP serves as an antenna, facilitating the transfer of absorbed light energy to R via triplet energy transfer (TET). Notably, the initial afterglow intensity and luminance of R increase by twofold and onefold, respectively, and the afterglow duration extends from 9 to 17 min. Furthermore, this study involves the preparation of a highly flexible film by mixing R@TCPP with high-density polyethylene (HDPE) to create a sound-controlled afterglow lamp. This innovative approach holds promising application prospects in flexible large-area luminescence, flexible wearables, and low-vision lighting.
RESUMEN
With the rapid advancements of Big Data and computer vision, many large-scale natural visual datasets are proposed, such as ImageNet-21K, LAION-400M, and LAION-2B. These large-scale datasets significantly improve the robustness and accuracy of models in the natural vision domain. However, the field of medical images continues to face limitations due to relatively small-scale datasets. In this article, we propose a novel method to enhance medical image analysis across domains by leveraging pre-trained models on large natural datasets. Specifically, a Cross-Domain Transfer Module (CDTM) is proposed to transfer natural vision domain features to the medical image domain, facilitating efficient fine-tuning of models pre-trained on large datasets. In addition, we design a Staged Fine-Tuning (SFT) strategy in conjunction with CDTM to further improve the model performance. Experimental results demonstrate that our method achieves state-of-the-art performance on multiple medical image datasets through efficient fine-tuning of models pre-trained on large natural datasets.
Asunto(s)
Bases de Datos Factuales , Humanos , Algoritmos , Interpretación de Imagen Asistida por Computador/métodos , Macrodatos , Procesamiento de Imagen Asistido por Computador/métodos , Diagnóstico por Imagen/métodosRESUMEN
Recent progress in two-dimensional ferroelectrics greatly expands the versatility and tunability in van der Waals heterostructure based electronics. However, the switching endurance issue that widely plagues conventional ferroelectrics in practical applications is hitherto unexplored for van der Waals layered ferroelectrics. Herein, we report the observation of unusual polarization fatigue behaviors in van der Waals layered CuInP2S6, which also possesses finite ionic conductivity at room temperature. The strong intertwinement of the short-range polarization switching and long-range ionic movement in conjunction with the van der Waals layered structure gives rise to unique morphological and polarization evolutions under repetitive electric cycles. With the help of concerted chemical, structural, lattice vibrational and dielectric analyses, we unravel the critical role of the synergy of ionic migration and surface oxidation on the anomalous polarization enhancement and the eventual polarization degradation. This work provides a general insight into the polarization fatigue characteristics in ionically-active van der Waals ferroelectrics and delivers potential solutions for the realization of fatigue-free capacitors.
RESUMEN
Chiral P,N-ligands are of great interest and importance in the fields of metal-catalyzed enantioselective transformations and have found numerous applications spanning drug and polymer synthesis. Here, modular assembly of diverse P-stereogenic and axially chiral phosphinooxazoles ligands is achieved through palladium-catalyzed asymmetric cleavage of C-P bond/intermolecular C-H bond functionalization in high atroposelectivities and diastereoselectivities of up to >99% ee and >25:1 dr. This protocol features broad substrate scope and provides an avenue for facile construction of new P-stereogenic and axially chiral phosphinooxazoles ligands directly from the phosphonium salts and benzoxazoles/benzothiazoles. Evaluation of the synthesized P-stereogenic and axially chiral phosphinooxazoles ligands in two model catalytic asymmetric reactions illustrates the potential of our strategy to access valuable chiral molecules.
RESUMEN
Background: Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms. Methods: P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing in vivo by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 1010 particles/ml) and high (4.56 x 1010 particles/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs in vitro. Then, miRNA microarrays and real-time quantitative PCR (RT-qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs. Results: Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. In vitro, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing. Conclusions: These results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.
RESUMEN
Titanium dioxide photocatalysts can break down pollutants using natural light. They possess notable light stability, chemical stability, and catalytic effects, thus leading to extensive research worldwide. However, the limited light absorption range of titanium dioxide and their inefficiencies in generating and transporting photogenerated carriers hinder the enhancement of their photocatalytic performance. In this study, we employ a femtosecond laser composite processing method to create an Ag-TiO2 nanoplate composite catalyst. This method doubles the catalytic efficiency compared with the structure processed solely with the femtosecond laser. The resulting Ag-TiO2 nanoplate composite catalysts show significant promise for addressing environmental and energy challenges, including the photodegradation of organic pollutants.
RESUMEN
OBJECTIVE: To determine the relationship between use of nebulized heparin and clinical outcomes in mechanically ventilated patients. METHODS: The Medline, Embase, Web of Science, Cochrane Library, and PubMed databases were searched for relevant randomized controlled trials (RCTs), published between database inception and May 2022. Primary outcomes were intensive care unit (ICU) length of stay and in-hospital mortality; secondary outcomes included duration of mechanical ventilation, ventilator-free days (VFDs) in 28 days, and length of hospitalization. The study protocol was registered on PROSPERO (registration No: CRD42022345533). RESULTS: A total of eight RCTs (651 patients) were included. Nebulized heparin was associated with reduced ICU length of stay (six studies; mean difference [MD] -1.10, 95% confidence interval [CI] -1.87, -0.33, I2 = 76%), reduced duration of mechanical ventilation (two studies; MD -2.63, 95% CI -3.68, -1.58, I2 = 92%) and increased VFDs in 28 days (two studies; MD 4.22, 95% CI 1.10, 7.35, I2 = 18%), without increased incidence of adverse events, such as bleeding; but was not associated with a reduction in length of hospitalization (three studies; MD -1.00, 95% CI -2.90, -0.90, I2 = 0%) or in-hospital mortality (five studies; odds ratio 1.10, 95% CI 0.69, 1.77, I2 = 0%). CONCLUSION: Nebulized heparin reduces ICU length of stay and duration of mechanical ventilation in mechanically ventilated patients, but has no effect on length of hospitalization or mortality.
Asunto(s)
Heparina , Respiración Artificial , Humanos , Respiración Artificial/efectos adversos , Heparina/uso terapéutico , Unidades de Cuidados Intensivos , Ventiladores Mecánicos , Tiempo de InternaciónRESUMEN
Chiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.
RESUMEN
Bletilla striata (Thunb. ex Murray) Rchb. F. (Orchidaceae) is an endangered traditional Chinese medicinal plant and has been traditionally used for hemostasis and detumescence in China (Wang et al. 2022). In March of 2021, during a field survey in Xuanwei city, Yunnan province, China, some B. striata plants with symptoms of plant dwarfing and leaf yellowing were observed. Roots of diseased plants presented numerous galls, typical symptoms of root-knot nematodes (RKNs) infection. The diseased area was approximately 66667 m2, showing a patchy disease distribution pattern. To identify the species of RKNs, females and eggs were isolated from galled tissue, and second-stage juveniles (J2s) were collected from eggs hatched. Nematodes were identified through comprehensive morphological and molecular methods. The perineal pattern of females is round to ovoid with a flat or moderately high dorsal arch and has two conspicuous lateral line striae. Morphological measurements of females (n=20) included body length (L) = 702.9 ± 70.8 (556.2-780.2) µm, body width (BW) = 404.1 ± 48.5 (327.5-470.1) µm, stylet length = 15.5 ± 2.2 (12.3-18.6) µm, distance from base of stylet to dorsal esophageal gland opening (DGO) = 3.7 ± 0.8 (2.1-4.9) µm. The morphometrics of J2s (n=20), L = 438.4 ± 22.6 (354.1-464.8) µm, BW = 17.4 ± 2.0 (12.9-20.8) µm, stylet length = 13.5 ± 0.4 (13.0-14.2) µm, DGO = 3.2 ± 0.6 (2.6-4.7) µm, and hyaline tail terminus = 12.3 ± 1.9 (9.6-15.7) µm. These morphological characteristics were similar to the original descriptions of Meloidogyne javanica (Rammah and Hirschmann 1990). DNA extraction was done 60 times, each from a different single females following the method of Yang et al. (2020). Amplification of ITS1-5.8S-ITS2 region of rDNA and the coxI region of mtDNA was done by using primers 18S/26S (5'-TTGATTACGTCCCTGCCCTTT-3'/5'-TTTCACTCGCCGTTACTAAGG-3') (Vrain et al. 1992) and cox1F/cox1R (5'-TGGTCATCCTGAAGTTTATG-3'/5'-CTACAACATAATAAGTATCATG-3') (Trinh et al. 2019) respectively. The PCR amplification program followed the method described by Yang et al. (2021). The ITS1-5.8S-ITS2 gene sequence (768 bp, GenBank Accession No. OQ091922) showed 99.35-100% identical to the known sequences of M. javanica (GenBank Accession Nos. KX646187, MW672262, KJ739710, KP901063, MK390613). The coxI gene sequence (410 bp, OQ080070) showed 99.75%-100% identical to the known sequences of M. javanica (OP646645, MZ542457, KP202352, KU372169, KU372170). Furthermore, M. javanica species-specific primers Fjav/Rjav (5'-GGTGCGCGATTGAACTGAGC-3'/5'-CAGGCCCTTCAGTGGAACTATAC-3') were used for PCR amplification. An expected fragment of approximately 670 bp was obtained, which was identical to that previously reported for M. javanica (Zijlstra et al. 2000). To verify pathogenicity of this nematode on B. striata, six 1.6-year-old tissue culture seedings of B. striata were maintained in 10-cm-diameter × 9-cm-high plastic pots containing a sterilized mixed soil (humus soil: laterite soil: perlite=3:1:1), and each plant was inoculated with 1000 J2s hatched from eggs of M. javanica. Three non-inoculated B. striata were used as the negative controls. All plants were placed in a greenhouse at approximately 14ï½26 â. After 90 days, the inoculated plants presented symptoms of leaf yellowing, and the roots with root knots identical to those observed in the fields. The root gall rating was 2 according to the 0-5 RKNs rating scale (Anwar and McKenry, 2002) and the reproductive factor (RF= final population/initial population) was 1.6. No symptoms or nematodes were observed on control plants. The nematode was reisolated and identified as M. javanica by morphological and molecular methods as above. To our knowledge, this is the first report of infection of M. javanica on B. striata. The infection of this economically important medicinal plant with M. javanica could pose a great threat to B. striata production in China, and further research will be necessary to develop control strategies.
RESUMEN
The study aimed to investigate the anti-tumor effects and underlying mechanisms of Enzalutamide (ENZ) and Arsenic trioxide (ATO) co-treatment on castration-resistant prostate cancer (CRPC). The effects on C4-2B cells were initially evaluated by colony formation assay, FACS analysis, and DNA fragmentation detection. Bioinformatics methods including mRNA-sequencing and gene enrichment analysis were used to screen the underlying target genes and pathways related to their actions. Western blot was employed to assess the expression levels of protein-related angiogenesis, apoptosis, DNA repair, and the screened genes. Finally, the effects were further verified in subcutaneous tumor models and tissue sections from the xenografts. It was found that not only could ENZ combination with ATO significantly inhibit cell proliferation and angiogenesis, but also induce cell arrest and apoptosis in C4-2B cells. In addition, interruption of the DNA damage repair-related pathways also occurred as a result of their combined effects. Western blot analysis further suggested that proteins involved in these pathways, especially P-ATR and P-CHEK1 were significantly reduced. In addition, their combination also inhibited the tumor growth of xenografts. Altogether, ENZ combination with ATO synergistically improved the therapeutic effects and suppressed CRPC progression through regulation of the ATR-CHEK1-CDC25C pathway.